WOMEN'S CANCER PROGRAM PROJECT SUMMARY The Women's Cancer Program (WCP) is a highly interactive, multidisciplinary research program co-led by Drs. Goetz, Degnim, and Bakkum-Gamez and composed of 61 basic and population scientists and clinical investigators from 14 departments and centers at Mayo Clinic in Rochester, MN; Arizona; and Florida. Its overarching goal is to advance the understanding of, and management strategies for, breast and gynecologic cancers. The substantial intraprogrammatic interactions reflect multidisciplinary WCP teams that focus on 4 major Specific Aims: 1) Genomics: to determine both host and tumor genetic alterations; 2) Biology: to define key mediators and pathways in the biology of women's cancers; 3) Advances in risk assessment: to define subgroups of women at increased risk; and 4) New clinical strategies: to develop and test innovative clinical strategies, especially based on discoveries from Specific Aims 1-3. The WCP's solid scientific base and opportunities for interactions have resulted in the renewal of the Mayo Clinic Breast and Ovarian SPOREs and new Stand Up to Cancer, DoD, and multiple R01 grants during the current project period. All of these grants support investigator-initiated clinical trials at Mayo Clinic and within clinical trial networks, including the Alliance for Clinical Trials, the Translational Breast Cancer Research Consortium, and the Stand Up to Cancer collaboration, with broad participation by Program members. Total direct peer-reviewed grant funding within the Program is $5.3M, with 56% from NCI. The Program has an additional $14.4M in direct, non-peer-reviewed funding. Since 2013, Program members have contributed 978 publications to the literature; 49% represent intraprogrammatic work, 29% reflect interprogrammatic collaborations, and 158 (16%) are in journals with an impact factor ?10. Some of this work has changed clinical practice, including reclassification of BRCA2 variants of unknown significance; development and implementation of a new breast cancer risk model; co-development of rucaparib, resulting in FDA approval and extension of PARP inhibitors beyond high-grade serous ovarian cancers with germline BRCA1 or BRCA2 mutations; and the development of Clinical Pharmacogenetics Implementation Consortium (CPIC) practice guidelines regarding the use of CYP2D6 genotype to guide tamoxifen treatment. WCP members benefit from the use of numerous Shared Resources, especially Biospecimens Accessioning and Processing, Pathology Research, Biostatistics, Survey Research, and the MCCC Clinical Research Office. To catalyze new and maintain ongoing collaborations, the Program has monthly scientific symposia and Breast and Gynecologic Cancer Disease Group meetings, weekly multidisciplinary conferences for breast and gynecologic cancer researchers, quarterly combined breast and gynecologic cancer conferences, and yearly multidisciplinary breast CME courses that rotate among the 3 Mayo sites. There is significant institutional and Cancer Center support for women's cancer?related research, education, outreach, and clinical practice endeavors.